Tangential-Flow Filtration for Virus Clearance

Vims clearance in excess of 10 -fold (4 log) is often difficult to validate from a single unit operation. Therefore, vims clearance from a number of different unit operations must be summed to determine the overall level of vims clearance for the purification train. Vims clearance can be by physical removal of the vims particles from the product or by inactivation. Regulatory authorities such as the U.S. Food and Dmg Administration (FDA) further specify that reduction factors for two-unit operations with the same mechanism of action may not be added. Furthermore, due to the high variability of infectivity assays, a reduction factor of less than 10-fold should not be included in the purification train. 

Large molecular weight cutoff UF membranes usually (1-3 x 10 Da Azari et al., 2000 Ogle and Azari, 2001) have been developed as vims filtration membranes. Vims filtration usually occurs close to the end of the purification train where the feed is relatively pure. Ideally, vims filtration membranes retain all vimses that may be present but show no rejection of the product. Vims filtration is most efficient when the vims particles are at least one order of magnitude larger than the product of interest. 

Today most vims filtration is conducted in normal flow mode (Bohonak and Zydney, 2005). The main advantage of tangential-flow filtration is the ability to suppress cake formation and the consequent decrease in permeate flux. This results in much larger feed volumes being filtered (capacity) before the module needs to be cleaned. 

During vims filtration, the vims particles are rejected by the membrane. Consequently, reuse of the membrane is not practical as one would need to validate removal of vims particles from the membrane. Sizing of vims filtration membranes depends on the clean 

Validation of parvovims clearance is often problematic as these nonenveloped vims particle are small (18-24 nm). Consequently, when the product of interest is large, use of normal flow filtration can lead to significant product rejection. Further validation of parvovims clearance by low pH or elevated temperamre is often not practical due to the high pH and thermal, stabUity of these vims particles. 

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